title: Adult-onset mastocytosis in the skin is highly suggestive of systemic mastocytosis.
abstract: Adult-onset urticaria pigmentosa/mastocytosis in the skin almost always persists throughout life. The prevalence of systemic mastocytosis in such patients is not precisely known. Bone marrow biopsies from 59 patients with mastocytosis in the skin and all available skin biopsies (n=27) were subjected to a meticulous cytological, histological, immunohistochemical, and molecular analysis for the presence of WHO-defined diagnostic criteria for systemic mastocytosis: compact mast cell infiltrates (major criterion); atypical mast cell morphology, KIT D816V, abnormal expression of CD25 by mast cells, and serum tryptase levels >20 ng/ml (minor criteria). Systemic mastocytosis is diagnosed when the major diagnostic criterion plus one minor criterion or at least three minor criteria are fulfilled. Systemic mastocytosis was confirmed in 57 patients (97%) by the diagnosis of compact mast cell infiltrates plus at least one minor diagnostic criterion (n=42, 71%) or at least three minor diagnostic criteria (n=15, 25%). In two patients, only two minor diagnostic criteria were detectable, insufficient for the diagnosis of systemic mastocytosis. By the use of highly sensitive molecular methods, including the analysis of microdissected mast cells, KIT D816V was found in all 58 bone marrow biopsies investigated for it but only in 74% (20/27) of the skin biopsies. It is important to state that even in cases with insufficient diagnostic criteria for systemic mastocytosis, KIT D816V-positive mast cells were detected in the bone marrow. This study demonstrates, for the first time, that almost all patients with adult-onset mastocytosis in the skin, in fact, have systemic mastocytosis with cutaneous involvement.
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Berezowska
authors.affiliation: Department of Dermatology and Allergology, University of Munich, Munich, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Flaig
authors.affiliation: Department of Dermatology and Allergology, University of Munich, Munich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Ruëff
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Walz
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.affiliation: Institute of Pathology, University of Schleswig Holstein, Lübeck, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Krokowski
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Kerler
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Petat-Dutter
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horny
authors.affiliation: Institute of Pathology, University of Munich, Munich, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001706:Biopsy; D001856:Bone Marrow Examination; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000473:pathology; D054705:Mastocytoma, Skin / Q000097:blood / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042282:Microdissection; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012867:Skin / Q000737:chemistry / Q000473:pathology; D053802:Tryptases / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases